Over in Health.SE, @faustus provided a couple of references to papers which suggest the use of Botulinum toxin A (BTA) - otherwise known as botox - to treat depression — Magid, et al. (2015a) and Finzi & Rosenthal, (2016)
Magid, et al. (2015a) states that
a single treatment of BTA in the glabellar region can produce a strong reduction in the symptoms of major depression
Figure: Improvement in BDI score. The figure shows absolute reduction in the BDI scores (14.3 vs. 5.1±standard error of the mean) from the baseline to the primary end point 6 weeks thereafter in the combined sample (n=134) for the BTA (n=59) and the placebo group (n=75), respectively.
whilst Finzi & Rosenthal, (2016) states that
In an initial case series, one of us (EF) injected BT into the frown of ten depressed patients, eight of whom went into remission after one treatment (Finzi and Wasserman, 2006; Finzi, 2013). The study was limited by its small size, lack of controls, and lack of blinding. In three subsequent randomized, double blind and placebo controlled trials, we and other researchers have found response rates of 50—60% in major depression, with about one third of patients going into remission (Wollmer et al. 2012; Finzi and Rosenthal, 2014; Magid et al. 2014, 2015b). BT showed antidepressant effects both when used as an ancillary treatment and by itself.
However, they then go on to say
How might injecting BT into the corrugator muscle influence the emotional brain? FMRI imaging has shown that subjects who received BT injections into their frown muscles had amygdala that were less responsive to negative stimuli (Hennenlotter et al. 2009). Recent work has confirmed that amygdala activity in response to angry faces was decreased when the frown muscles were paralyzed by BT injection. Furthermore, amygdala activity returned to its original inducible state after the effects of the BT injection had worn off, confirming that BT reversibly severed afferent feedback from the corrugator muscle to the amygdala (Kim et al. 2014).
With the decrease in amygdala activity in response to angry faces, am I correct in thinking that this could have a detrimental effect with regard to the flight/flight response in potentially dangerous situations?
Finzi, E. (2013). Antidepressant effects of botulinum toxin A: scientific rationale. Journal of psychiatry & neuroscience: JPN, 38(5), E29. PMCID: PMC3756121
Finzi, E., & Rosenthal, N. E. (2014). Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial. Journal of psychiatric research, 52, 1-6. DOI: 10.1016/j.jpsychires.2013.11.006
Finzi, E., & Rosenthal, N. E. (2016). Emotional proprioception: treatment of depression with afferent facial feedback. Journal of psychiatric research, 80, 93-96. DOI: 10.1016/j.jpsychires.2016.06.009
Finzi, E., & Wasserman, E. (2006). Treatment of depression with botulinum toxin A: a case series. Dermatologic Surgery, 32(5), 645-650. DOI: 10.1111/j.1524-4725.2006.32136.x
Hennenlotter, A., Dresel, C., Castrop, F., Ceballos-Baumann, A. O., Wohlschläger, A. M., & Haslinger, B. (2008). The link between facial feedback and neural activity within central circuitries of emotion—New insights from Botulinum toxin–induced denervation of frown muscles. Cerebral Cortex, 19(3), 537-542. DOI: 10.1093/cercor/bhn104
Kim, M. J., Neta, M., Davis, F. C., Ruberry, E. J., Dinescu, D., Heatherton, T. F., ... & Whalen, P. J. (2014). Botulinum toxin-induced facial muscle paralysis affects amygdala responses to the perception of emotional expressions: preliminary findings from an ABA design. Biology of mood & anxiety disorders, 4(1), 11. DOI: 10.1186/2045-5380-4-11
Magid, M., Reichenberg, J. S., Poth, P. E., Robertson, H. T., LaViolette, A. K., Kruger, T. H., & Wollmer, M. A. (2014). Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. The Journal of clinical psychiatry, 75(8), 837-844. DOI: 10.4088/JCP.13m08845
Magid, M., Finzi, E., Kruger, T. H. C., Robertson, H. T., Keeling, B. H., Jung, S., ... & Wollmer, M. A. (2015a). Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials. Pharmacopsychiatry, 25(06), 205-210. DOI: 10.1055/s-0035-1559621
Magid, M., Finzi, E., Kruger, T. H. C., Robertson, H. T., Keeling, B. H., Jung, S., ... & Wollmer, M. A. (2015b). Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials. Pharmacopsychiatry, 48(6), 205-210. DOI: 10.1055/s-0035-1559621
Wollmer, M. A., de Boer, C., Kalak, N., Beck, J., Götz, T., Schmidt, T., ... & Sönmez, D. (2012). Facing depression with botulinum toxin: a randomized controlled trial. Journal of psychiatric research, 46(5), 574-581. DOI: 10.1016/j.jpsychires.2012.01.027